Silverman's golden drug makes him NU's golden ticket

    Lyrica is one of two approved treatments for fibromyalgia. It also treats epilepsy and is among the most effective treatments for painful seizures. It was a big seller in hard times for Pfizer, raking in $1.2 billion in sales in 2006. And the scientist who developed this drug is Dr. Richard Bruce Silverman of the Northwestern Chemistry department.

    Lyrica royalties helped Northwestern’s endowment grow more than the endowments of the other 20 richest universities during the 2009 fiscal year. Now that the European Union has approved the drug for generalized anxiety disorder, investors predict profits from the drug will climb even higher.

    In many ways, Silverman’s work on Lyrica was the culmination of a groundbreaking career in medical research. Silverman’s research focuses on nervous system disorders, a field that led him to the development of pregabalin, the chemical that Pfizer later marketed as Lyrica.

    Lyrica’s development contained a couple of serendipitous discoveries. Silverman set out to prevent seizures by balancing certain chemicals in the brain. He discovered a molecule that was able to activate the enzyme L-glutamate decarboxylase, the enzyme that produces GABA, an inhibitory neurotransmitter and an important molecule to block convulsions.

    The first serendipitous outcome: Lyrica, although it achieved Silverman’s original aims, was effective for a reason entirely different from his initial goal of producing more GABA. The second serendipitous observation: the chemical happens to be the correct shape to be transported directly into the brain. About 90% of each dose gets to where it’s needed. Needless to say, pharmaceutical companies found Lyrica extremely interesting.

    The school’s Lyrica royalties, along with a gift from Silverman, funded the new $63 million Silverman Hall for Molecular Therapeutics and Diagnostics.

    Silverman Hall is designed to house the same sort of research that led to Silverman’s Lyrica. The building will house researchers in chemistry, biology and engineering, increasing collaboration, interaction and idea-sharing across related disciplines. Normally, researchers in different fields work in separate buildings and rarely interact with one another, however the building features a pair of two-story “interaction spaces” designed to burst the social bubbles that traditionally exist within scientific disciplines.

    North by Northwestern emailed the busy professor to talk about his latest achievements and his plans for the future.

    I understand pregabalin is an extremely significant new treatment. At what point in your research did you know that pregabalin would be an important development in the industry?
    As an adjunct therapy for epilepsy, it was an important new drug, but when it was shown also to be effective in the treatment of neuropathic pains and fibromyalgia, it had a much larger potential patient base and became a much more important contribution. Nerve pains and fibromyalgia are horrendous problems; the quality of life is vastly increased when they are relieved.

    What went through your mind when you first discovered this chemical’s effectiveness?
    My group did not discover its effectiveness for treatment of disease. We do basic research. When the group at Parke-Davis Pharmaceuticals showed such high efficacy as an anticonvulsant agent in mice, I was amazed. This compound was sent to Parke-Davis to be tested as an anticonvulsant, so I thought it would be effective; I just didn’t realize how effective it would be.

    What do you hope Silverman Hall will contribute to the school?
    I believe Silverman Hall already has had a major impact on Northwestern in terms of the senior faculty that we have been able to hire away from other universities because of the fantastic research opportunities in this beautiful new building. Silverman Hall should spawn many more important collaborations, and I believe will be home to significant discoveries in therapeutics and diagnostics.

    What do you see as being important in the future of the medical industry?
    New advances in treating poorly treated or untreated neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, ALS, Huntington’s disease, and cerebral palsy will take place in the future. New diagnostics for identifying diseases early in their progression also will become available. All of these breakthroughs could actually occur at Northwestern.

    Faculty members at Northwestern already are starting to make significant breakthroughs using nanotechnology for tissue regeneration and disease diagnostics.

    Stem-cell research?
    Now that scientists in the United States have been allowed to work more actively in the area of stem cell research since Obama’s tenure, there should start to be new discoveries in the use of stem cells for tissue regeneration, including conditions resulting from spinal cord and brain injuries and disease. Northwestern is very active in all of these areas.

    What do you hope to accomplish in the future? Any long-term research or development goals?
    My research focuses mainly on central nervous system disorders, including Parkinson’s disease, ALS, Huntington’s disease, cerebral palsy, epilepsy and addiction. We have more than one compound in animal testing. If I get lucky enough, I would be delighted to have another compound make it to clinical trials…..and beyond.

    Do you have any advice to students considering chemistry as a profession?
    If you enjoy chemistry, it is a very rewarding career, either in industry or academia. The job market is very variable from year to year, so do not decide to enter or not enter the field based on what is happening when you are beginning.

    Do you remember the first time you decided you wanted to pursue a career in chemistry?
    After having a chemistry set at age 8.


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